PROJECT SUMMARY/ABSTRACT Bisphenol A (BPA) is commonly used in plastics and epoxies, and has been shown to leach from these materials under certain conditions. Although it provides desirable material properties, numerous studies have shown adverse health effects after exposure, particularly in developing fetuses, infants, and children. In this work, we aim to develop and utilize a high-throughput platform for assessing the relative toxicity of BPA and BPA substitutes (both known and novel) in neurodevelopment using Schmidtea mediterranea planaria as a novel model system. Planaria are small freshwater flatworms. They possess a central nervous system consisting of a bilobed ?brain? called the cephalic ganglia and two ventral nerve cords that traverse the length of the body and support a peripheral nerve ladder. Most remarkably, these animals have the ability to regenerate their entire body, including the central nervous system, from almost any piece of the organism due to a large population of pluripotent adult stem cells called neoblasts. Previous work by the investigative team has shown that planarian head regeneration is impeded by exposure to alcohol or BPA, which suggests that neurodevelopmental toxicity in planaria may be analogous to that in humans. One major goal of this exploratory research is to categorize the effects of BPA and BPA substitutes on neuroregeneration and neurodevelopmental processes by developing and utilizing a high-throughput platform for assessing the relative toxic effects of BPA and BPA substitutes, including those effects that are dependent upon timing, duration, and dosage of exposure. Additionally, in this project, the investigators aim to develop and produce novel BPA substitutes that are derived from renewable resources, and to assess the relative toxicity of these alternatives using the high-throughput planaria testing platform. The ultimate objective of these substitutes is that the novel compound provides equivalent or superior material properties with reduced toxicity and the environmental advantages associated with development using sustainable practices and renewable resources. Taken together, the results of this work will enhance our understanding of neurodevelopmental toxicity by BPA and BPA substitutes, and provide potential novel BPA substitutes that could have equivalent or superior material properties and reduced toxicity.